Patent GB-596868-A (GB)
Title: Improvements in or relating to the synthesis of sulphonamide compounds
IPC: C07D241/22
Filed: 1945-02-05
Abstract: Sulphonamide compounds are obtained by treating a 4-acylaminobenzenesulphonyl halide with an amino-pyrazine of the formula <FORM:0596868/IV/1> where R1 and R2 are the same or different and are alkyl groups or aryl groups or one of them is hydrogen and the other is an alkyl group or aryl group, or together they constitute a part of a cyclic hydrocarbon.  Specified compounds are 2-amino-5-alkyl, -5-aryl-, -6-alkyl-, -6-aryl-, -5 : 6-dialkyl-, -5 : 6-diaryl- or -5 : 6-phenanthrapyrazine.  The acylamino group of the reaction product is hydrolysed to form an amino group.  The amino-pyrazines are prepared from the correspondingly substituted dihydroxy - pyri - midopyrazines, hydrolysing to obtain aminopyrazine-carboxylic acids and decarboxylating the latter. In examples: (1) 2-amino-5-methylpyrazine, in pyridine, is treated with 4 - acetylaminobenzenesulphonyl chloride to isolate 2-(4-acetylaminobenzenesulphonamido)-5-methylpyrazine, which is hydrolysed by heating with either alcoholic hydrochloric acid or aqueous sodium hydroxide to the corresponding 2 - (4 - aminobenzenesulphonamido) - compound; (2) 2-amino-6-methylpyrazine is treated as in (1) to isolate 2-(4-acetylaminobenzenesulphonamido) - 6 - methylpyrazine, hydrolysed by aqueous sodium hydroxide to the 2-(4-aminobenzenesulphonamido)-compound; (3) 2-amino-5 : 6-dimethylpyrazine is treated as in (1) to isolate a -(4-acetylaminobenzenesulphonamido)-5 : 6-dimethylpyrazine, hydrolysed as in (2); (4) 2 - amino - 5 : 6 - diphenylpyrazine; and (5) 2-amino-phenanthrapyrazine are treated as in (1), respectively to isolate the corresponding 2 - (4 - acetylaminobenzenesulphonamido)-compounds, which are hydrolysed by dilute hydrochloric acid.  2-Amino-5-methylpyrazine is obtained by heating under reflux a mixture of 2-carboxy-5-methylpyrazine, methanol, anhydrous sodium sulphate and concentrated sulphuric acid, saturating the filtrate with ammonia and adding ether to precipitate 2-carboxyamino-5-methylpyrazine, which is decarboxylated by treating with chlorine and aqueous caustic alkali.  2-Amino-6-methylpyrazine is obtained by heating under reflux a mixture of methyl glyoxal (prepared from isonitrosoacetone and 50 per cent sulphuric acid) and 2 : 6-dihydroxy-4 : 5-diaminopyrimidine, the resulting 2 : 4-dihydroxy - 7 - methylpyrimidopyrazine being heated with aqueous sodium hydroxide and acidified to isolate 2-amino-3-carboxy-6-methylpyrazine, which is decarboxylated by heating under reflux with 80 per cent sulphuric acid.  2-Amino-5 : 6-dimethylpyrazine is obtained by heating 2 : 6-dihydroxy-4 : 5-diaminopyrimidine with diacetyl in aqueous 4 per cent hydrochloric acid, the resulting 2 : 4 - dihydroxy - 6 : 7 - dimethylpyrimidopyrazine being heated in an autoclave with aqueous sodium hydroxide and the product diluted and acidified with hydrochloric acid to isolate 2-amino-3-carboxy-5 : 6-dimethylpyrazine, which is decarboxylated by heating under reflux with 80 per cent sulphuric acid.  2-Amino-5 : 6-diphenylpyrazine is obtained by heating 2 : 6-dihydroxy-4 : 5-diaminopyrimidine and benzil with aqueous alcoholic ammonia, the resulting 2 : 4 - dihydroxy - 6 : 7 - diphenylpyrimidopyrazine being heated under reflux with aqueous sodium hydroxide and the product then treated with barium chloride to obtain the barium salt of 2-amino-3-carboxy-5 : 6-diphenylpyrazine, which is heated with aqueous hydrochloric acid and methanol to obtain 2 - amino - 3 - carboxy - 5 : 6 - diphenylpyrazine, finally decarboxylated by heating under reflux with 80 per cent sulphuric acid.  2-Amino-phenanthrapyrazine is obtained by condensing 9 : 10-phenanthraquinone and 2 : 6-dihydroxy-4 : 5-diaminopyrimidine by refluxing in a solvent containing a dilute acid or base, or in glacial acetic acid, and heating the resulting 2 : 4 - dihydroxy - 6 : 7 - phenanthrapyrimido - pyrazine with aqueous sodium hydroxide in a bomb, the product being acidified to about pH 2 to precipitate 2-amino-3-carboxy-phenanthrapyrazine, which is decarboxylated by heating.